Safety and Efficacy of AST-120 in Patients With Non-Constipating Irritable Bowel Syndrome

Irritable Bowel Syndrome Clinical Trial

Official title:

A Double-Blind, Randomized, Placebo-Controlled Multicenter Study to Assess the Safety and Efficacy of AST-120 in Patients With Non-Constipating Irritable Bowel Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00583128
• Other study ID #: AST014
• Status: Completed
• Phase: Phase 2
• First received: December 20, 2007
• Last updated: June 2, 2014
• Start date: August 2007
• Est. completion date: June 2010

Study information

• Verified date: June 2014
• Source: Ocera Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to evaluate the safety and effectiveness of the experimental drug AST-120 in treating patients with non-constipating IBS. The study will test whether or not patients receiving AST-120 experience at least a 50% reduction in the number of days with abdominal pain compared to placebo.

Description:

Patients experiencing non-constipating IBS will be randomized to one of two arms in the study: the experimental drug AST-120 or placebo. Patients will take 2g of AST-120 or placebo three times per day for eight weeks. After the 8 week course, patients will receive an additional 8 weeks single blind treatment, after a one week washout period.

The experimental drug AST-120 is composed of black, odorless spherical carbon particles in 2g sachets (aluminum foil pouches). The placebo consists of microcrystalline cellulose spheres, Celphere CP-305 stained to match the appearance of AST-120, in 2g sachets (aluminum foil pouches). Both AST-120 and placebo are oral (taken by mouth) preparations. Both are tasteless. To take the product, patients will tear open the sachet, drop the contents directly on their tongue and wash it down with 8 ounces of water.

Patients will be expected to participate in up to 10 visits, approximately three by telephone and the remainder of visits are in-clinic. At these visits, patients will undergo a number of tests including: hematology panel, lactose intolerance testing, physical exams, pregnancy tests, evaluations based on the following scales: The Bristol Stool Scale, IBS Severity Scale, IBS Quality of Life, SCL-90R.

Provided the patient has been stable for eight weeks prior to their baseline visit, they will be allowed to take the following medications: drugs that inhibit gastric secretion (histamine blockers, proton pump inhibitors), benzodiazepines and Imidazopyridines (short acting, nonbenzodiazepine hypnotics) for sleep (dose must be consistent with the use of a sleep agent) aspirin at a cardiovascular prophylactic dose (75-150 mg/day) and paracetamol. Antidepressants for non-IBS symptoms are allowed. Loperamide will be permitted as a rescue for diarrhea only when patients are experiencing at least 3 liquid or soft stools in one day. However, Loperamide is prohibited during the two week screening period.

Patients will not be allowed to take the following medications whilst on trial and these therapies must have been discontinued by at least two weeks prior to their baseline visit: probiotics, neuroleptics, antidepressants for IBS symptoms, daytime tranquilizers, prokinetics, spasmolytics, analgesics, other investigational agents and any over-the-counter medications.

Patient will be required to keep a diary during the study

Recruitment information / eligibility

• Status: Completed
• Enrollment: 117
• Est. completion date: June 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Body weight = 40 kg;

• Recurrent abdominal pain or discomfort for three or more days per month for the last three months which meets Rome III criteria for non-constipating IBS;

• Patients on a stable diet for at least eight weeks;

• Patients = 50 years of age with a negative screening colonoscopy in the last five years;

• Able and willing to comply with all protocol procedures for the planned duration of the study;

• Able and willing to understand, sign and date an informed consent document, and authorize access to protected health information,

• Females must be postmenopausal, surgically incapable of bearing children, or practicing a reliable method of birth control (intrauterine devices, spermicide and barrier) (Hormonal contraceptives are NOT regarded as adequate for the purpose of this trial.) Partner/spouse sterility may also qualify at the Investigator's discretion. Females of child-bearing potential must have a negative urine pregnancy test at baseline.

Exclusion Criteria:

• Constipating IBS;

• History of untreated lactose intolerance;

• History of colonic or major abdominal surgery (colectomy, for example);

• Active (untreated) Thyroid disease;

• Current diagnosis of major depression or psychosis;

• Known positive stool cultures for Clostridium difficile or other pathogens;

• Any condition necessitating the administration of analgesics (except paracetamol), probiotics, neuroleptics, antidepressants for IBS symptoms, daytime tranquilizers, prokinetics or spasmolytic medications;

• Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling;

• Other major physical or major psychiatric illness within the last six months that in the opinion of the investigator would affect the patient's ability to complete the trial;

• Uncontrolled systemic disease such as diabetes;

• Patients undergoing chemotherapy for the treatment of cancer;

• Known hypersensitivity or contraindication to any component of the test product (study drugs) or diagnostics used;

• Participation in another study within eight (8) weeks prior to the study;

• Unable to attend all visits required by the protocol;

• Female patients must be excluded if they are pregnant, breast feeding, or planning to become pregnant during the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Irritable Bowel Syndrome
• Syndrome

Intervention

Drug:
• AST-120
oral, sachet, 2 grams three times daily for 8 weeks
• Celphere® CP-305
oral, placebo, sachet, 2 grams three times daily for 8 weeks

Locations

Country	Name	City	State
Belgium	AZ St. Lucas Assebroek	Assebroek
Belgium	Zuid-Oost Limburg Campus St. Jan	Genk
Belgium	UZ Leuven	Leuven
Belgium	UCL St. Luc	Woluwe
United States	Michael Epstein, MD	Annapolis	Maryland
United States	Madeleine DuPree, MD	Boynton Beach	Florida
United States	Chevy Chase Clinical Research	Chevy Chase	Maryland
United States	Ohio Gastroenterology and Liver Institute	Cincinnatti	Ohio
United States	Long Island Gastrointestinal Research Group	Great Neck	New York
United States	LeBauer Research Associates	Greensboro	North Carolina
United States	Peters Medical Research, LLC	High Point	North Carolina
United States	Breco Research LTD	Houston	Texas
United States	Clinical Research Associates	Huntsville	Alabama
United States	Wisconsin Center for Advanced Research	Milwaukee	Wisconsin
United States	Oklahoma Foundation for Digestive Disease	Oklahoma City	Oklahoma
United States	Northern California Research	Sacramento	California
United States	Medical Center for Clinical Research	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Ocera Therapeutics

Countries where clinical trial is conducted

United States,  Belgium, 

References & Publications (5)

Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006 Apr;130(5):1377-90. Review. — View Citation

Schuster MM. Defining and diagnosing irritable bowel syndrome. Am J Manag Care. 2001 Jul;7(8 Suppl):S246-51. Review. — View Citation

Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers AM, Janssens J. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut. 2006 Aug;55(8):1095-103. Epub 2006 Jan 9. — View Citation

Tack JF, Miner PB Jr, Fischer L, Harris MS. Randomised clinical trial: the safety and efficacy of AST-120 in non-constipating irritable bowel syndrome - a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011 Oct;34(8):868-77. doi: 10.1111/ — View Citation

Wood JD. Histamine, mast cells, and the enteric nervous system in the irritable bowel syndrome, enteritis, and food allergies. Gut. 2006 Apr;55(4):445-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of patients who achieve at least a 50% reduction in the number of days with abdominal pain during the final 2 weeks of the double-blind treatment course.		Eight weeks	No
Primary	Safety endpoint is adverse events (AEs) deemed possibly, probably, or definitely related to treatment with investigational product during the double-blind treatment course.		8 weeks	Yes
Secondary	Percent change in the IBS QOL score.		Eight weeks	No
Secondary	Percent change in HADS score.		8 weeks	No
Secondary	Percent change in Bristol Scale score.		8 weeks	No
Secondary	Percent change in individual items in the IBS Symptom Severity questionnaire.		8 weeks	No
Secondary	Durability of effect after the first eight weeks of treatment.		8 weeks	No
Secondary	Change in clinical laboratory tests from Baseline to Week 8 and to Week 18.		8 weeks	Yes
Secondary	Any adverse event occurring after Week 8.		8 weeks	Yes
Secondary	Physical examinations, vital signs (blood pressure, heart rate, respiration and temperature).		8 weeks	Yes